Familial Dysautonomia (FD, OMIM #223900) is an hereditary sensory and autonomic neuropathy, mostly affecting persons of Ashkenazi descent. Symptoms vary from patient to patient, and include insensitivity to pain (due to loss of nociceptors and thermoreceptors in the Dorsal Root Ganglia (DRG) unstable blood pressure and body temperature, frequent pneumonia resulting in chronic lung diseases, poor growth, chronic kidney diseases, optic neuropathy leading to progressive visual loss and gait ataxia. FD patients typically can expect a shortened lifespan, and currently have a 50% probability of surviving beyond the age of 40.
The disease is known to be the result of a mutation in the gene inhibitor of kappa B kinase complex-associated protein (IKBKAP, Anderson et al., 2001), which in turn results in tissue-specific reductions of IKAP protein. The exact function of IKAP is not yet fully understood. The protein appears to be required for modification of tRNAs during translation and may function directly or indirectly in the transcription (Hawkes et al., 2002; Karlsborn et al., 2014; Kim et al., 2002).
Current pharmacological treatment of FD is focussed on the management of the various symptoms of the disease (Palma et al., 2014).
There is thus an urgent need to find a treatment of FD that acts at a neuronal level by modulating the effect of the IKAP deficiency which is responsible for the syndrome.